Biallelic germline mutations in the base excision repair gene MYH have been shown to predispose to a proportion of multiple colorectal adenomas and cancer.
Recessively inherited mutations in the base excision repair gene MYH have recently been associated with predisposition to colorectal adenomas and cancer.
Thus, we compared the carrier frequency of MUTYH IVS10-2A>G heterozygote in the APC mutation negative cases with that in 115 controls over 70 years of age who showed no apparent clinical manifestations of cancer and claimed that they had no history of cancer at the time of enrollment.
Recessively inherited mutations in the base excision repair gene MYH have recently been associated with predisposition to colorectal adenomas and cancer in materials selected for occurrence of multiple adenomas.
Further studies are necessary for the assessment of MUTYH not only in melanoma but also other cancer types with the same embryonic origin, in the context of larger arrays studies of genes involved in DNA stability or integrity.
Biallelic germline mutations in the base excision repair gene MYH have been reported in patients with multiple colorectal adenomas and cancer and in sporadic FAP patients not showing a detectable APC germline mutation.
The expression of MUTYH protein in colorectal adenomas or cancer was studied by IHC using three different (1 polyclonal and 2 monoclonal) antibodies in six samples from patients with biallelic MUTYH mutations, in three samples from patients with a single MUTYH mutation, and in 11 samples from patients without MUTYH mutations.
Although the number of adenomas appears to be dependent on the number of mutated MYH alleles present in a patient, little is known on the relation of this number with cancer risk.
MYH-associated polyposis is an inherited autosomal recessive disease, linked to biallelic germline MYH mutations, which predisposes to the development of multiple colorectal adenomas and cancer.
An additional 9 individuals carried mutations in other genes linked to high lifetime risks of cancer (5 had mutations in APC, 3 had bi-allelic mutations in MUTYH, and 1 had a mutation in STK11); all of these patients met NCCN criteria for Lynch syndrome testing.
The relevance of these results will be discussed to define the role of specific human mutations in colorectal cancer risk together with the possible role of MUTYH inactivation in sporadic cancer.
The human DNA repair gene MUTYH, whose mutational loss causes a colorectal polyposis and cancer predisposition, contains three alternative first exons.
Age at onset of polyposis and age at surgery were 10-15 years delayed for carriers of MUTYH mutations; cancer at diagnosis was frequent, and extracolonic manifestations were diagnosed in the majority of MUTYH-positive families.
In vitro analysis of Q324HMUTYH expressed in insect cells showed that it has reduced enzyme activity similar to that of the known cancer variant G382D.